Process for preparation of 1,4-benzodioxane derivative

Abstract

A novel process for preparing a 1,4 benzodioxane derivative shown by the formula (1) which is a useful intermediate of circulatory drugs and drugs for psychoneurosis, characterized in sulfonating a phenoxypropanediol with a sulfonyl halide, eliminating the protective group, and then cyclizing the sulfonated compound by treating with a base followed by, if necessary, further sulfonation. ##STR1## In the above formula, R.sup.1 is H, RSO.sub.2, R is alkyl, phenyl which may be substituted with alkyl, R.sup.2, R.sup.3, R.sup.4 are H, halogen, OH, nitro, cyano, formyl, COOH, alkoxycarbonyloxy, alkyl, alkoxy, haloalkyl, N,N-dialkylamino, alkylcarbonyl, alkoxycarbonyl, phenyl which may be substituted by alkyl, etc.22

Claims

1. A process for preparing a 1,4-benzodioxane derivative as shown by the following formula (1) ##STR7## wherein R.sup.1 is hydrogen atom or RSO.sub.2 in which R is C.sub.1 -C.sub.4 alkyl, or phenyl which may be substituted by C.sub.1 -C.sub.4 alkyl, R.sup.2, R.sup.3 and R.sup.4 are respectively hydrogen, halogen, hydroxy, nitro, cyano, formyl, carboxyl, alkoxycarbonyloxy having 1-4 carbon atoms in the alkyl portion, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 haloalkyl, N,N-di C.sub.1 -C.sub.4 alkylamino, alkylcarbonyl having 1-4 carbon atoms in the alkyl portion, alkoxycarbonyl having 1-4 carbon atoms in the alkyl portion or phenyl which may be substituted by C.sub.1 -C.sub.4 alkyl, or two groups among R.sup.2, R.sup.3, and R.sup.4 may be combined together to constitute methylenedioxy on adjacent carbon atoms, or two groups among R.sup.2, R.sup.3 and R.sup.4 may be combined together to constitute phenyl on adjacent carbon atoms, wherein a diol compound as shown by the following formula (2) ##STR8## wherein R.sup.2, R.sup.3 and R.sup.4 are same as defined above, R.sup.5 is benzyl, allyl, o-nitrobenzyl, t-butyldimethylsilyl or benzyloxycarbonyl, or R.sup.5 may be constituted methylenedioxy, isopropylidenedioxy, cyclohexylidenedioxy or diphenylmethylenedioxy together with oxygen atom in the hydroxy or the R.sup.5 O-group, provided that when any one of R.sup.2, R.sup.3 and R.sup.4 is hydroxy and the hydroxy is bound on the carbon atom adjacent to the carbon atom substituted by R.sup.5 O-group, is reacted with a sulfonyl halide in the presence of a base to obtain a sulfonated compound as shown by the following formulae (3) and/or (4) ##STR9## wherein R, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 are the same as defined above, and after elimination of the protective group R.sup.5 of the sulfonated compound, the compound is cyclized by treating with a base.

2. The process for preparing a 1,4-benzodioxane derivative claimed in claim 1 wherein, after the elimination of the protective group on a mixture of a compound shown by the formula (3) and a compound shown by the formula (4), the deprotected compound is subjected to cyclization under a base, and the cyclized compound shown by the formula (1) is further reacted with a sulfonyl halide.

3. The process for preparing a 1,4-benzodioxane derivative claimed in claim 1 wherein an optically active 1,4-benzodioxane derivative is prepared by using an optically active diol shown in formula (2).

4. The process for preparing a 1,4-benzodioxane derivative claimed in claim 1 wherein the sulfonyl halide is toluenesulfonyl chloride or C.sup.1 -C.sup.4 alkyl sulfonyl chloride.

5. The process for preparing a 1,4-benzodioxane derivative claimed in claim 4 wherein the sulfonyl halide is toluenesulfonyl chloride.

6. The process for preparing a 1,4-benzodioxane derivative claimed in claim 1 in which the protective group R.sup.5, wherein R.sup.5 is benzyl, allyl or benzyloxycarbonyl, on the sulfonated compound shown by formula (3) or (4) is eliminated under hydrogenation with palladium/carbon in an organic solvent.

7. The process for preparing a 1,4-benzodioxane derivative claimed in claim 1 wherein a catechol derivative shown by the following formula (7) ##STR10## wherein R.sub.2, R.sup.3, R.sup.4 and R.sup.5 are the same defined in claim 1, is reacted with 3-chloro-1,2-propanediol shown by the following formula (8) ##STR11## in the presence of a base to obtain a diol compound shown by the formula (2).

8. The process for preparing an optically active 1,4-benzodioxane derivative claimed in claim 3 wherein a catechol derivative shown by the following formula (7) ##STR12## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same defined above, is reacted with an optically active 3-chloro-1,2-propanediol shown by the following formula (8) ##STR13## in the presence of a base to obtain the optically active diol compound shown by the formula (2).